• Anemia, intestinal obstruction, preoperative chemotherapy, acidosis, and albumin <30 g/L are independent risk factors for sepsis in colorectal cancer patients complicated with gastrointestinal perforation.
What is known and what is new?
• Perforation of the digestive tract can lead to complex intra-abdominal infection, leading to peritonitis, intra-abdominal abscess, and progression to sepsis and septic shock.
• Colorectal cancer combined with gastrointestinal perforation can lead to poor prognosis, and this model can effectively identify patients at a high risk of sepsis.
What is the implication, and what should change now?
• Intervention through the timely identification of high-risk patients and associated risk factors may be beneficial in improving patient outcomes; however, further clinical studies are still needed.
The incidence of colorectal cancer ranks third among all malignant tumors (1), and some patients may also have gastrointestinal perforation (2,3). The most common site of gastrointestinal perforation is the sigmoid colon, which accounts for about 50%, followed by the ascending colon, descending colon, and rectum. Abdominal pain is a common clinical symptom of gastrointestinal perforation; since colorectal cancer is more common in middle-aged and elderly patients and the elderly are relatively insensitive to peritonitis symptoms, patients can have no peritonitis symptoms in the early stage of gastrointestinal perforation, resulting in delayed diagnosis and treatment. Therefore, severe abdominal infection and even sepsis may be found upon diagnosis of colorectal cancer (4). Colorectal perforation is a life-threatening acute abdomen, accounting for up to 20% of patient deaths after emergency surgery (5). At present, there is a paucity of studies exploring the risk factors for sepsis in colorectal cancer patients complicated with gastrointestinal perforation and its impact on prognosis, and thus, we designed this study. We present the following article in accordance with the TRIPOD reporting checklist (available at https://jgo.amegroups.com/article/view/10.21037/jgo-23-205/rc).
From January 2016 to December 2017, 126 patients with colorectal cancer complicated with gastrointestinal perforation were collected retrospectively and continuously from the Dazu Hospital of Chongqing Medical University. The patients were divided into a sepsis group (n=56) and a control group (n=70) according to whether they developed sepsis or not.
Inclusion criteria: (I) colorectal cancer; (II) combined with digestive tract perforation; (III) age ≥18 years old; (IV) received treatment at the Dazu Hospital of Chongqing Medical University with complete clinical data. Exclusion Criteria: (I) Combined with other malignant tumors; (II) recurrent colorectal cancer; (III) insufficiency in important organs such as liver and kidney; (IV) combined with infection in other parts; (V) distant metastasis; (VI) lost to follow-up.
This retrospective clinical study was performed in accordance with the Declaration of Helsinki (as revised in 2013) and was approved by the Ethics Committee of Dazu Hospital of Chongqing Medical University (No. c2022-03-132). The requirement for informed consent was waived due to the retrospective nature of the study. The patient inclusion flowchart is shown in Figure 1.
(I) Colorectal cancer: All patients were diagnosed with colorectal cancer based on colonoscopy or postoperative pathological diagnosis. (II) Gastrointestinal perforation: Abdominal X-ray showed free gas in the abdomen, and colorectal perforation was confirmed during surgery. (III) Sepsis: Abdominal drainage fluid was retained, and bacterial culture confirmed the existence of abdominal infection. Moreover, if the sepsis-related sequential organ failure assessment score increased by ≥2 points from baseline, the patient was diagnosed with sepsis (6).
All patients were given symptomatic supportive care, such as electrocardiogram monitoring, early fluid resuscitation, anti-infection, and maintenance of electrolyte balance after admission (6). At the same time, emergency surgery was performed. After surgery, symptomatic supportive therapy such as anti-infection treatment could be continued, and if necessary, organ function support therapy, such as mechanical ventilation and continuous hemofiltration, could also be given. After surgery, according to the pathological results, it was decided whether to administer chemotherapy. The patients were followed up for 5 years, and the 5-year survival rate was observed.
The following data were collected: age, sex, course of abdominal pain, body mass index, diabetes, hypertension, tumor location, tumor size, degree of tumor cell differentiation, tumor cell type, lymph node metastasis, peripheral invasion, vascular tumor thrombus, anemia, intestinal obstruction, preoperative chemotherapy, acidosis, and preoperative albumin.
SPSS26.0 (IBM, Armonk, NY, USA) was used to complete the data analysis, and P<0.05 indicated that the difference was statistically significant (two-tailed). The measurement data, such as age and tumor size, of the two groups were expressed by the mean ± standard deviation, and the differences between the two groups were analyzed by an independent sample t-test. The gender, diabetes status, and other counting data of the two groups were expressed by n (%), and the chi-square test was used to analyze the differences between the two groups.
Multivariate logistics regression analysis was used to explore the risk factors for sepsis in patients with colorectal cancer complicated with gastrointestinal perforation. The receiver operating characteristic (ROC) curve was used to analyze the predictive value of albumin in colorectal cancer patients complicated with gastrointestinal perforation. R4.0.3 statistical software was used to establish a sepsis prediction model in colorectal cancer patients complicated with gastrointestinal perforation.
Comparison of the clinical features between the two groups
Compared with the control group, the proportion of patients with abdominal pain >8 h, anemia, intestinal obstruction, preoperative chemotherapy, acidosis, and preoperative albumin <30 g/L was significantly increased in the sepsis group (P<0.05) (Table 1).
|Variables||Sepsis group (n=56)||Control group (n=70)||t/χ2 value||P value|
|Age (years), mean ± standard deviation||61.63±9.08||63.63±8.90||1.245||0.216|
|Gender, n (%)||0.000||1.000|
|Male||32 (57.14)||40 (57.14)|
|Female||24 (42.86)||30 (42.86)|
|Abdominal pain course (h), mean ± standard deviation||17.05±6.90||12.67±5.90||3.842||0.000|
|Duration of abdominal pain >8 h, n (%)||47 (83.93)||47 (67.14)||4.627||0.031|
|Body mass index (kg/m2), mean ± standard deviation||24.06±2.58||23.94±2.33||0.309||0.758|
|Diabetes, n (%)||6 (10.71)||8 (11.43)||0.016||0.899|
|Hypertension, n (%)||9 (16.07)||15 (21.43)||0.579||0.447|
|Location of the tumor, n (%)||2.308||0.129|
|Colon||43 (76.79)||40 (57.14)|
|Rectum||13 (23.21)||30 (42.86)|
|Tumor size (cm), mean ± standard deviation||6.21±1.86||6.24±1.84||0.083||0.934|
|The degree of differentiation, n (%)||0.838||0.360|
|Low or undifferentiated||12 (21.43)||20 (28.57)|
|Medium to high differentiation||44 (78.57)||50 (71.43)|
|Tumor cell type, n (%)||0.041||0.839|
|Adenocarcinoma||51 (91.07)||63 (90.00)|
|Non-adenocarcinoma||5 (8.93)||7 (10.00)|
|Lymph node metastases, n (%)||0.250||0.617|
|Yes||46 (82.14)||55 (78.57)|
|No||10 (17.86)||15 (21.43)|
|Peripheral invasion, n (%)||0.295||0.587|
|Yes||21 (37.50)||23 (32.86)|
|No||35 (62.50)||47 (67.14)|
|Vascular tumor thrombus, n (%)||0.188||0.664|
|Yes||18 (32.14)||20 (28.57)|
|No||38 (67.86)||50 (71.43)|
|Anemia, n (%)||4.599||0.032|
|Yes||29 (51.79)||23 (32.86)|
|No||27 (48.21)||47 (67.14)|
|Ileus, n (%)||7.431||0.006|
|Yes||15 (26.79)||6 (8.57)|
|No||41 (73.21)||64 (91.43)|
|Preoperative chemotherapy, n (%)||6.930||0.008|
|Yes||12 (21.43)||4 (5.71)|
|No||44 (78.57)||66 (94.29)|
|Acidosis, n (%)||16.665||0.000|
|Yes||42 (75.00)||27 (38.57)|
|No||14 (25.00)||43 (61.43)|
|Preoperative albumin (g/L), mean ± standard deviation||26.80±4.68||31.24±4.55||5.369||0.000|
|Preoperative albumin <30 g/L, n (%)||39 (69.64)||24 (34.29)||15.557||0.000|
Risk factor analysis of sepsis in colorectal cancer patients complicated with gastrointestinal perforation
Multivariate logistic regression analysis showed that anemia, intestinal obstruction, preoperative chemotherapy, acidosis, and albumin <30 g/L were independent risk factors for sepsis in colorectal cancer patients complicated with gastrointestinal perforation (P<0.05) (Table 2).
|Variables||B-value||Standard error||Wald value||P value||Relative risk (95% CI)|
|Duration of abdominal pain >8 h||0.724||0.518||1.953||0.162||2.064 (0.747–5.700)|
|Preoperative chemotherapy||1.858||0.762||5.940||0.015||6.414 (1.439–28.584)|
|Albumin <30 g/L||0.939||0.451||4.330||0.037||2.558 (1.056–6.197)|
CI, confidence interval.
Predictive value of albumin in colorectal cancer patients complicated with gastrointestinal perforation
Albumin was valuable in predicting the absence of sepsis in colorectal cancer patients complicated with gastrointestinal perforation, and the area under the curve was 0.751 (95% confidence interval: 0.666–0.835) (Figure 2).
Establishment and validation of a sepsis prediction model in colorectal cancer patients complicated with gastrointestinal perforation
R4.0.3 statistical software was used for statistical analysis. The dataset was randomly divided into a training set and a validation set, with a sample size of 88 in the training set and 38 in the validation set. Anemia, intestinal obstruction, preoperative chemotherapy, acidosis, and albumin were included in the predictive model. A nomogram and ROC curve were established, and the areas under the ROC curves in the training and verification sets were 0.857 (95% confidence interval: 0.776–0.938) and 0.735 (95% confidence interval: 0.568–0.902), respectively. In the validation set, the model was tested with Hosmer-Lemeshow Goodness-of-Fit, with a chi-square value of 10.274 and a P value of 0.246 (Figures 3,4).
Prognosis of colorectal cancer patients complicated with gastrointestinal perforation
Compared with the control group, the 5-year survival rate of patients in the sepsis group was significantly reduced (35.71% vs. 57.14%, P=0.017).
Colorectal cancer combined with gastrointestinal perforation is a clinically common, yet critical and fatal disease. If the infection is not controlled in time, it can develop into sepsis, multiple organ failure, and eventually lead to death. It was confirmed by previous studies that postoperative infection after colorectal surgery have been associated with negative economic impact, increased morbidity, extended postoperative hospital stay, readmission, sepsis, and death (7,8). Therefore, it is crucial to identify colorectal cancer patients complicated with gastrointestinal perforation who are at a high risk of sepsis. We designed the present study, which showed that anemia, intestinal obstruction, preoperative chemotherapy, acidosis, and albumin <30 g/L were independent risk factors for sepsis in colorectal cancer patients complicated with gastrointestinal perforation (P<0.05). The model established in the present study was valuable in predicting sepsis in colorectal cancer patients complicated with gastrointestinal perforation, with an area under the ROC curve of 0.857 (95% confidence interval: 0.776–0.938).
Digestive tract tumors can cause anemia in several ways: (I) Secretion of cytokines inhibits hematopoietic function; (II) digestive tract tumors lead to malnutrition, resulting in a serious lack of vitamins, iron, folic acid, and other hematopoietic raw materials; and (III) trans-gastrointestinal bleeding. Therefore, it is more common for colorectal cancer patients to have anemia, especially in patients with colorectal cancer in the middle and advanced stages (9-12). Patients with anemia have decreased immune function and are prone to sepsis (13-15). If colorectal cancer grows into the intestinal lumen, it can cause intestinal obstruction. Intestinal edema will occur in patients with intestinal obstruction, resulting in an increase in intestinal permeability, water-electrolyte disturbance, and intestinal flora displacement, leading to sepsis (16). Intestinal permeability is increased in patients with preoperative chemotherapy, and intestinal edema is obvious in some patients. Moreover, chemotherapy can suppress the body’s immunity, resulting in the spread of infection (17). Acidosis refers to the accumulation of acidic substances in the blood and tissues in the body, while its essence is the increased concentration of hydrogen ions in the blood. Acidosis includes respiratory acidosis and metabolic acidosis; it is the embodiment of tissue ischemia and hypoxia, indicating insufficient tissue perfusion. If acidosis is not corrected in time, it can promote the progression of sepsis (18,19). Albumin has numerous biological functions in patients with infection: (I) Maintenance of hemodynamic stability and reduction of tissue edema; and (II) it is an important protein involved in the body’s immunity. When albumin is reduced, its effect is limited, so patients become prone to sepsis. Albumin should be supplemented in time in gastrointestinal perforation patients with a low albumin level (20-23). Finally, according to the literature, following colorectal cancer procedures, postoperative sepsis is significantly more common among patients over 65 years old, ASA score >2 (7). However, no similar results were observed in the present study, which may be due to the fact that only patients with gastrointestinal perforation were included in this study.
In addition, to more efficiently identify people at high risk of sepsis, we built a nomogram predictive model. The results showed that this model was valuable in predicting sepsis in colorectal cancer patients complicated with gastrointestinal perforation. The prognoses of many diseases are multifactorial, and thus, the prognostic value of using a single factor to predict patients is limited (24-27). In recent years, some scholars have pointed out that a nomogram prediction model can be built to synthesize multiple biological indicators, which can more effectively predict the prognosis of patients, and the value of this model has been confirmed in patients with sepsis (28-32).
This was a retrospective clinical study, and the incidence of gastrointestinal perforation was relatively low due to the popularity of colonoscopy, etc. Therefore, the total number of cases included in this study was relatively insufficient.
Colorectal cancer patients complicated with gastrointestinal perforation have a high incidence of sepsis, which can lead to a poor prognosis. The model presented in this study can effectively identify patients at a high risk of sepsis. Intervention through timely identification of high-risk patients and risk factors may be beneficial in improving patient outcomes; however, further clinical studies are still needed.
Reporting Checklist: The authors have completed the TRIPOD reporting checklist. Available at https://jgo.amegroups.com/article/view/10.21037/jgo-23-205/rc
Data Sharing Statement: Available at https://jgo.amegroups.com/article/view/10.21037/jgo-23-205/dss
Peer Review File: Available at https://jgo.amegroups.com/article/view/10.21037/jgo-23-205/prf
Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jgo.amegroups.com/article/view/10.21037/jgo-23-205/coif). The authors have no conflicts of interest to declare.
Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. This retrospective clinical study was performed in accordance with the Declaration of Helsinki (as revised in 2013) and was approved by the Ethics Committee of Dazu Hospital of Chongqing Medical University (No. c2022-03-132). The requirement for informed consent was waived due to the retrospective nature of the study.
Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.
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(English Language Editor: A. Kassem)